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Reorientation of membrane dipoles during nerve excitation
BULLETIN OF MATHElYIATICAL BIOLOGY
VOLUME35, I973
LETTER
TO
THE
EDITOR
I~EORIENTATION OF ]~/[E1KBRANE DIPOLES DURING ~ E R V E EXGITATION
Wei (1971) attempts to explain the process of nerve excitation in terms of quant u m transitions of membrane dipoles. The idea is interesting and worth pursuing but the illustrative example in the second last paragraph was an unfortunate choice. The trimethylamine group in phosphatidyl choline (lecithin), 4-
--N-~-(CH~)a, cannot become a free ion in solution because the nitrogen atom is covalently bonded to a fourth carbon atom. +
Wei suggests that the group --N~(CH~)~ is similar to the gas trimethylamine, N(CH~) 3. The analogy in structure of the trimethylamine group in lecithin with gaseous N H 3 and N(CH3)3 is incorrect. The suggested 180 ° reversal of dipole moment b y the nitrogen atom of lecithin is not applicable since the trimethylamine group is not a free ion or a symmetric top. Dipole reorientation may have a role to play in membrane excitation notwithstanding this erroneous example. Hill etal. (1969) discuss dipole reorientation and dielectric dispersion while Meakins (1959) has studied dipole orientation for ketones and ethers in a solid hydrocarbon solution. These studies have been done on reasonably simple chemical systems so we are not entirely free to extrapolate to the more complex structures of biological membranes. The structure of membrane phospholipids and their charge distribution m a y allow dipole interactions. Phosphatidyl choline can be considered a zwitterion since there m a y be unmasked charged groups at the nitrogen and oxygen molecules near the polar end of the molecule. The net charge is a function of p H and of ion concentration. Aspects of the ionic structure of lecithin in monolayers have been discussed by Shah and Schulman (1967). (This work has been questioned recently b y Colacicco, 1972). From these properties it is highly likely that membrane conformation is influenced b y molecular dipoles and the local electrical fields that interact with them. It m a y be possible to measure 417
418
LETTER TO THE EDITOR
a n g u l a r distortions in phospholipids b y m e a n s of infrared s p e c t r o p h o t o m e t r y . As an order of m a g n i t u d e a p p r o x i m a t i o n let us consider a c o m p l e t e l y different system, the deformations of bonds in a crystal lattice and the r e s u l t a n t splitting of infrared a n d R a m a n bands. H a r v e y a n d McQuaker (1971) h a v e r e p o r t e d v3/,~ splittings in I~H~ and h a v e presented a g r a p h of w a v e n u m b e r versus angular distortion. F o r the v i b r a t i o n v4(E ) the distortion in four angles is 0.6 ° cm -1 a n d 1.2 ° cm -1 in two angles. The splittings which correspond to other frequencies a n d s y m m e t r i e s are of the same order of m a g n i t u d e . R e c e n t l y we h a v e r e p o r t e d shifts of a few e m - 1 in the infrared s p e c t r u m of nerve during conduction, Sherebrin (1972), Sherebrin, MacClement a n d F r a n k o (1972). The bonds for which we h a v e observed frequency shifts are in t h e v i c i n i t y of molecular dipoles and we p o s t u l a t e t h a t there is a S t a r k effect during excitation. While a b o n d distortion of a p p r o x i m a t e l y one degree m a y be small, it m a y be sufficient to alter the binding of an ion, say Ca + +, a n d control t h e m e m b r a n e p e r m e a b i l i t y to N a + and K +. LITERATURE Colaciceo, G. 1972. "Lipid Monolayers: Surface Potential of Dipalmitoyllecithin with respect to Ion Sorption and Ca + + Binding." Biochim. Biophys. Acta, 266, 313-319. Harvey, K. B. and N. R. McQuaker. 1971. '°Force Fields for Crystalline BH~ and NH + Ions." ,7. Chem. Phys., 55, 4396-4399. Hill, N. E., W. E. Vaughan, A. H. Price and IV[.Davies. 1969. Dielectric Properties and Molecular Behaviour. London: Van Nostrand Reinhold Co., p. 406. Meakins, R . J . 1959. "The Magnitude of the Dielectric Absorption in Solid Alipbatic Longcham Compounds." Trans..Faraday Soc., 55, 1701-1704. Shah, D. O. and J. H. Shulman. 1967. "The Ionic Structure of Lecithin Monolayers." J. Lipid t~es., 8, 227-233. Sherebrin, M.H. 1972. "Changes in Infrared Spectrum of Nerve during Excitation." Nature "New Biol., 235, 122-124. , B. A. E. MacClement and A. J. Franko. 1972. °:Electric-Field-Induced Shifts in the Infrared Spectrum of Conducting Nerve Axons." Biophys. J., 12, 977-989. Wei, L . Y . 1971. "Quantmn Theory of Nerve Excitation." Bull. IYlath. Biophysics, 33, 187-194. M. H, SHEREBRIN Biophysics Dept., University of Western Ontario, London 72, Canada I~ECEIVED 4-26-72
VOLUME35, I973
LETTER
TO
THE
EDITOR
I~EORIENTATION OF ]~/[E1KBRANE DIPOLES DURING ~ E R V E EXGITATION
Wei (1971) attempts to explain the process of nerve excitation in terms of quant u m transitions of membrane dipoles. The idea is interesting and worth pursuing but the illustrative example in the second last paragraph was an unfortunate choice. The trimethylamine group in phosphatidyl choline (lecithin), 4-
--N-~-(CH~)a, cannot become a free ion in solution because the nitrogen atom is covalently bonded to a fourth carbon atom. +
Wei suggests that the group --N~(CH~)~ is similar to the gas trimethylamine, N(CH~) 3. The analogy in structure of the trimethylamine group in lecithin with gaseous N H 3 and N(CH3)3 is incorrect. The suggested 180 ° reversal of dipole moment b y the nitrogen atom of lecithin is not applicable since the trimethylamine group is not a free ion or a symmetric top. Dipole reorientation may have a role to play in membrane excitation notwithstanding this erroneous example. Hill etal. (1969) discuss dipole reorientation and dielectric dispersion while Meakins (1959) has studied dipole orientation for ketones and ethers in a solid hydrocarbon solution. These studies have been done on reasonably simple chemical systems so we are not entirely free to extrapolate to the more complex structures of biological membranes. The structure of membrane phospholipids and their charge distribution m a y allow dipole interactions. Phosphatidyl choline can be considered a zwitterion since there m a y be unmasked charged groups at the nitrogen and oxygen molecules near the polar end of the molecule. The net charge is a function of p H and of ion concentration. Aspects of the ionic structure of lecithin in monolayers have been discussed by Shah and Schulman (1967). (This work has been questioned recently b y Colacicco, 1972). From these properties it is highly likely that membrane conformation is influenced b y molecular dipoles and the local electrical fields that interact with them. It m a y be possible to measure 417
418
LETTER TO THE EDITOR
a n g u l a r distortions in phospholipids b y m e a n s of infrared s p e c t r o p h o t o m e t r y . As an order of m a g n i t u d e a p p r o x i m a t i o n let us consider a c o m p l e t e l y different system, the deformations of bonds in a crystal lattice and the r e s u l t a n t splitting of infrared a n d R a m a n bands. H a r v e y a n d McQuaker (1971) h a v e r e p o r t e d v3/,~ splittings in I~H~ and h a v e presented a g r a p h of w a v e n u m b e r versus angular distortion. F o r the v i b r a t i o n v4(E ) the distortion in four angles is 0.6 ° cm -1 a n d 1.2 ° cm -1 in two angles. The splittings which correspond to other frequencies a n d s y m m e t r i e s are of the same order of m a g n i t u d e . R e c e n t l y we h a v e r e p o r t e d shifts of a few e m - 1 in the infrared s p e c t r u m of nerve during conduction, Sherebrin (1972), Sherebrin, MacClement a n d F r a n k o (1972). The bonds for which we h a v e observed frequency shifts are in t h e v i c i n i t y of molecular dipoles and we p o s t u l a t e t h a t there is a S t a r k effect during excitation. While a b o n d distortion of a p p r o x i m a t e l y one degree m a y be small, it m a y be sufficient to alter the binding of an ion, say Ca + +, a n d control t h e m e m b r a n e p e r m e a b i l i t y to N a + and K +. LITERATURE Colaciceo, G. 1972. "Lipid Monolayers: Surface Potential of Dipalmitoyllecithin with respect to Ion Sorption and Ca + + Binding." Biochim. Biophys. Acta, 266, 313-319. Harvey, K. B. and N. R. McQuaker. 1971. '°Force Fields for Crystalline BH~ and NH + Ions." ,7. Chem. Phys., 55, 4396-4399. Hill, N. E., W. E. Vaughan, A. H. Price and IV[.Davies. 1969. Dielectric Properties and Molecular Behaviour. London: Van Nostrand Reinhold Co., p. 406. Meakins, R . J . 1959. "The Magnitude of the Dielectric Absorption in Solid Alipbatic Longcham Compounds." Trans..Faraday Soc., 55, 1701-1704. Shah, D. O. and J. H. Shulman. 1967. "The Ionic Structure of Lecithin Monolayers." J. Lipid t~es., 8, 227-233. Sherebrin, M.H. 1972. "Changes in Infrared Spectrum of Nerve during Excitation." Nature "New Biol., 235, 122-124. , B. A. E. MacClement and A. J. Franko. 1972. °:Electric-Field-Induced Shifts in the Infrared Spectrum of Conducting Nerve Axons." Biophys. J., 12, 977-989. Wei, L . Y . 1971. "Quantmn Theory of Nerve Excitation." Bull. IYlath. Biophysics, 33, 187-194. M. H, SHEREBRIN Biophysics Dept., University of Western Ontario, London 72, Canada I~ECEIVED 4-26-72